{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:41:17Z","timestamp":1789663277504,"version":"4.0.1"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mammalian target of rapamycin (mTOR) plays crucial roles in activation and differentiation of diverse types of immune cells. Although several lines of evidence have demonstrated the importance of mTOR-mediated signals in CD4+ T cell responses, the involvement of mTOR in CD8+ T cell responses is not fully understood. In this study, we show that a class IV semaphorin, SEMA4A, regulates CD8+ T cell activation and differentiation through activation of mTOR complex (mTORC) 1. SEMA4A\u2212\/\u2212 CD8+ T cells exhibited impairments in production of IFN-\u03b3 and TNF-\u03b1 and induction of the effector molecules granzyme B, perforin, and FAS-L. Upon infection with OVA-expressing Listeria monocytogenes, pathogen-specific effector CD8+ T cell responses were significantly impaired in SEMA4A\u2212\/\u2212 mice. Furthermore, SEMA4A\u2212\/\u2212 CD8+ T cells exhibited reduced mTORC1 activity and elevated mTORC2 activity, suggesting that SEMA4A is required for optimal activation of mTORC1 in CD8+ T cells. IFN-\u03b3 production and mTORC1 activity in SEMA4A\u2212\/\u2212 CD8+ T cells were restored by administration of recombinant Sema4A protein. In addition, we show that plexin B2 is a functional receptor of SEMA4A in CD8+ T cells. Collectively, these results not only demonstrate the role of SEMA4A in CD8+ T cells, but also reveal a novel link between a semaphorin and mTOR signaling.<\/jats:p>","DOI":"10.4049\/jimmunol.1403038","type":"journal-article","created":{"date-parts":[[2015,6,27]],"date-time":"2015-06-27T08:26:16Z","timestamp":1435393576000},"page":"934-943","source":"Crossref","is-referenced-by-count":43,"title":["mTOR Complex Signaling through the SEMA4A\u2013Plexin B2 Axis Is Required for Optimal Activation and Differentiation of CD8+ T Cells"],"prefix":"10.1093","volume":"195","author":[{"given":"Daisuke","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University , Suita City, Osaka 565-0871 ,","place":["Japan"]},{"name":"Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine , Suita City, Osaka 565-0871 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